Modulation of the Rcs-mediated signal transfer by conformational flexibility. (19th November 2008)

• Record Type: Journal Article
• Authors: Rogov, Vladimir V.; Schmöe, Kerstin; Löhr, Fank; Rogova, Natalia Yu.; Bernhard, Frank; Dötsch, Volker
• Is Part Of: Biochemical Society transactions. Volume 36:Number 6(2008)
• Page Start: 1427
• Page End: 1432
• Publication Date: 2008-11-19
• Subjects: BeF3− activation -- histidine phosphotransferase domain -- NMR solution structure -- phosphoreceiver domain -- Rcs phosphorelay system -- sensor kinase; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0361427
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : The Rcs (regulator of capsule synthesis) signalling complex comprises the membrane-associated hybrid sensor kinases RcsC and RcsD, the transcriptional regulator RcsB and the two co-inducers RcsA and RcsF. Acting as a global regulatory network, the Rcs phosphorelay controls multiple cellular pathways including capsule synthesis, cell division, motility, biofilm formation and virulence mechanisms. Signal-dependent communication of the individual Rcs domains showing histidine kinase, phosphoreceiver, phosphoryl transfer and DNA-binding activities is characteristic and essential for the modulation of signal transfer. We have analysed the structures of core elements of the Rcs network including the RcsC-PR (phosphoreceiver domain of RcsC) and the RcsD-HPt (histidine phosphotransfer domain of RcsD), and we have started to characterize the dynamics and recognition mechanisms of the proteins. RcsC-PR represents a typical CheY-like α/β/α sandwich fold and it shows a large conformational flexibility near the active-site residue Asp 875 . NMR analysis revealed that RcsC-PR is able to adopt preferred conformations upon Mg 2+ co-ordination, BeF3 − activation, phosphate binding and RcsD-HPt recognition. In contrast, the α-helical structure of RcsD-HPt is conformationally stable and contains a recognition area in close vicinity to the active-site His 842 residue. Our studies indicate the importance of protein dynamics and conformational exchange for the differential response to the variety of signals perceived by complex regulatory networks.